International Journal of Research and Review
Vol.7; Issue: 5; May 2020
Website: www.ijrrjournal.com
E-ISSN: 2349-9788; P-ISSN: 2454-2237
Review Paper
Acne Vulgaris in Adults: A Brief Review on
Diagnosis and Management
Febyan1, Krisnhaliani Wetarini2
1
Department of Medicine, Bhayangkara Hospital, Denpasar, Bali, Indonesia.
Department of Medicine, Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia.
2
Corresponding Author: Febyan
ABSTRACT
Acne vulgaris is a chronic skin disease with an
inflammatory condition of the skin affecting the
pilosebaceous glands. Four concepts of
pathogenesis lead to the formation of acne
vulgaris, such as sebum production, follicular
skin,
microbial
colonization
by
Propionibacterium
acnes
bacteria,
and
inflammatory mediators. The diagnosis of acne
vulgaris is dependent on the identification of
lesions using classification from the American
Academy Dermatology. Acne management is
exceptionally diverse, including monotherapy or
a combination of various agents that have a role
in suppressing the anti-inflammatory and
antibacterial
activities
following
the
multifactorial causes of acne.
Keywords: acne, adults, skin diseases,
Propionibacterium acne, management
INTRODUCTION
Acne vulgaris (AV) is a chronic skin
disease with an inflammatory condition of
the skin affecting the pilosebaceous glands.
[1]
Acne does not only occur in teenagers but
also adults population. [2] The study of the
Global Burden of Disease (GBD) reported
that AV affects about 85% of young adults
aged 12-25 years. [3] In the United States
(US), one of the top three most prevalent
skin disease is acne vulgaris. [4] Based on a
study from Singapore, acne was found
dominantly in about 88% of adolescents
aged 13 to 19 years. Acne vulgaris is
commonly found in adolescent males, while
in the post-adolescent period, it is more
frequent in females. [5] Sahala et al. reported
that Indonesia is one of the countries with a
high prevalence of skin diseases; including
AV. [6] Sitohang et al. reported 1,525 new
acne cases in outpatient visits from the
cosmetic dermatology division of Cipto
Mangunkusumo General Hospital, making
AV as the second most common skin
disease from dermato-venerology outpatient
clinics. [7]
Symptoms of AV are known to be
affecting the occurrence of depression,
leading to a lower quality of life in its
[8]
patients,
especially
adolescents.
Psychological comorbidities, including
depression and anxiety, have been
associated with AV. The potential for postinflammatory hyperpigmentation (PIH) and
scarring into adulthood affected later quality
of life as well. [8] A previous study by
Yentzer et al. reported 8.8% of female
patients with depression associated with
AV. [9] Thus, more patients are presenting to
physicians seeking proper treatment. The
objective of this review is to describe the
diagnosis and management of AV
accurately to prevent further complications.
CONCEPT OF ETIOLOGY AND
PATHOGENESIS
Four concepts of pathogenesis lead
to the formation of AV, including the
increase and alteration of sebum production,
alteration of follicular skin keratinization
that leads to comedones, colonization by
Propionibacterium acnes, and inflammatory
processes that involve innate and acquired
immunity. [10] Bronsnick et al. reported an
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Febyan et.al. Acne vulgaris in adults: a brief review on diagnosis and management
association between AV and consumption
of milk or low-fat milk product. [11] Melnik
et al. also found that high consumption of
high glycemic food products and milk are
hypothesized to increase the levels of
insulin and serum insulin growth factor-1,
leading to comedogenesis, sebaceous
lipogenesis, follicular inflammation, and
androgenic stimulation. All these factors
which promote to AV processes pathology.
[12]
Sebum Production
The production of sebum is
controlled by androgen and testosterone
hormones. [9,12] The initial pathology is
initially triggered by androgen hormone. [12]
In patients with severe acne, an increased
level of dehydroepiandrosterone sulfate
(DHEAS) but low sex hormone-binding
globulin (SHBG) levels were found, which
further induce the elevation of the androgen
level. Significant elevation of DHEAS,
androstenedione, and SHBG level may
occur both in female and male patients.
Sebum production subsequently plays a role
in the pathophysiology of acne to induce the
inflammatory process. [13]
Follicular Hyperkeratinization
In acne pathophysiology, there is an
essential role of one type of fatty acid
known as linoleic acid. The decreased levels
of linoleic acid in the skin may cause
hyperkeratinization or hypercornification of
follicular
cells
in
the
skin.
Hyperkeratinization occurs when follicular
cells undergo cohesion and cannot be shed
to the surface of the skin, causing
microcomedones that are subsequently
forming into acne. [14]
Microbial Colonization by
Propionibacterium acnes
Propionibacterium acne has been
implicated in the pathophysiology of AV.
Genomic observation identifies that P.acne
is about 2.5 Mb in size. [15] P.acne is an
anaerobic Gram-positive commensal of
normal skin. This bacterium contains
ribosome-rich cytoplasm and peptidoglycan
that build the cell wall layer. The
overgrowth of P.acne is ideal in comedones
because of the presence of lipase enzyme
that functions to degrade the lipids on the
skin follicle and subsequently become their
nutritional source. [16] Free fatty acids
produced by lipase are secreted from P.acne
and activate the comedogenic and acnegenic
factors in sebaceous follicles, leading to the
irritation of the follicular walls and the
surrounding dermis. This process causes
follicular
rupture,
which
induces
inflammation by releasing low molecular
weight chemotactic factors. These factors
diffuse through the thinned follicular
epithelium and attract neutrophils, creating
the local inflammation reaction. [17]
Additionally, P.acne also produces protease
and hyaluronidase, induces the keratinocyte
growth,
and
activates
matrix
metalloproteinase-toll
like
receptor
pathway. [18]
Role of Inflammatory Mediators
The fourth and final factor involved
in the pathogenesis of acne is the
inflammatory reaction. [17] Inflammatory
mediators lead to the formation of
microcomedones through lymphocytic
infiltration mediated by CD4+ T-cells and
CD68+ macrophages. Interleukin 1 alpha
(IL-1a), Th17 pathway, dendritic cells are
also present in the mechanism of AV. [19]
Interleukin-1a has been found as an initial
inflammatory mediators in comedogenesis.
[1]
The invasion of neutrophils can also
increase the reactive oxygen species (ROS)
level as the result of microbial colonization.
This condition leads to the lysis of the
invaded
cell
and
increases
more
inflammatory mediators that induce the
acne. [20]
DIAGNOSIS AND EVALUATION
The diagnosis of AV is generally
established by identifying of quantity and
morphology of the lesions. Their
morphologies are divided into the noninflammatory comedones, termed as open
(blackheads) or closed (whiteheads) and the
inflammatory lesions, termed as papules,
pustules, cyst, or nodules. American
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Febyan et.al. Acne vulgaris in adults: a brief review on diagnosis and management
Academy Dermatology (AAD) classified
the severity of AV into mild, moderate, and
severe (See Figure 1). Mild AV is
characterized by the presence of a few to
several papules and pustules, but no
nodules. Moderate AV is characterized by
several papules and pustules, along with a
few nodules. Severe AV is characterized by
numerous or extensive papules and pustules,
as well as multiple nodules. [10]
Figure. 1 Classification of Acne Vulgaris. [21]
DIFFERENTIAL DIAGNOSIS
There are several of differential diagnosis of AV, such as (1) acne rosacea, which is
commonly observed in middle age or later in life, (2) folliculitis and boils, which often
present with pustular lesions similar to acne, (3) milia, which is a small non-follicular keratin
papules that may be confused with whiteheads, and (4) pityrosporum folliculitis, which more
predominates on the trunk. [22]
MANAGEMENT
According to the American Academy Dermatology (AAD), the management of AV consists
of two principles i.e., the first-line and alternative treatment (Table 1). [23]
Type
of
Treatment
First-line
medication
Mild Acne

Table 1. Consideration of Management of Acne Vulgaris [10, 23]
Moderate Acne
Severe Acne
Topical combination therapy*; 
Oral antibiotic and topical
or
combination
therapy*;
or


Oral antibiotic, topical retinoid,
and
benzoyl
peroxide; 
Oral isotretinoin

or

Oral antibiotic, topical retinoid,
benzoyl peroxide, and topical
antibiotic
Alternative

Add topical retinoid or benzoyl 
Consider
alternative 
Consider change in oral
medication
peroxide (in case one is not used
combination
therapy*;
antibiotic;
already);
or
or
or

Consider change in oral 
Add
combined
oral
antibiotic;
contraceptive
or
oral

Consider alternative retinoid;
or
spironolactone
(female
or
patients);

Add
combined
oral

Consider topical dapsone
or
contraceptive
or
oral
spironolactone
(female 
Consider oral isotretinoin
patients);
or

Consider oral isotretinoin
* Topical combination therapy (benzoyl peroxide and antibiotic agent; retinoid and benzoyl peroxide; or retinoid, benzoyl peroxide, and an
antibiotic) may be prescribed as a fixed-dose combination product or as separate components. This recommendation for the management of
AV was modified from Zaenglein et al. [10]
Topical retinoid;
or
Benzoyl peroxide; or
Topical combination therapy*

Topical Agents
The main focus on acne treatment is topical
drugs. The most common topical
medications for acne include benzoyl
peroxide, clindamycin, and retinoids. [23-25]
Benzoyl Peroxide
Benzoyl peroxide (BP) is commonly
prescribed topical medications for AV. It
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Febyan et.al. Acne vulgaris in adults: a brief review on diagnosis and management
mainly reduces the colonization of P. acnes
and inflammatory acne lesions. It also has
keratolytic and sebostatic effects without a
concern for the development of drugresistant bacteria. Benzoyl peroxide is a
bactericidal agent, has stable formulation in
treating comedonal acne. It has several
concentrations ranging from 2.5%, 5%, and
10%. The Food and Drug Administration
(FDA) classified that BP as pregnancy risk
category C. [24, 25]
Retinoids
Topical retinoids are effective firstline therapy against comedonal and
inflammatory acne. These topical are
vitamin A derivates, and the binding of
retinoids to their receptors, these agents may
reduce hyperkeratinization and decreases
adhesion. [26] Based on in vivo observation,
these agents have demonstrated antiinflammatory activity. Topical retinoids
may reduce microcomedones and mature
comedos, promote desquamation of
follicular
epithelium,
and
reduce
inflammatory mediators. [27]
Clindamycin
Another commonly used topical
antibiotic regiment for the treatment of AV
is clindamycin. It works by targeting the 50s
subunit of bacterial ribosomes and
interfering with the protein synthesis,
thereby exerting antibacterial effects.
Clindamycin also has the effect of
suppressing inflammation, which can be
induced by P. acnes. [28] Some studies
showed that clindamycin could inhibit the
expression of proinflammatory cytokines,
such as interleukin 1, interleukin 6, and
tumor necrosis factor. Although this
regiment has been shown to display
considerable success in the treatment of AV,
it is rarely used as a monotherapy because
of the high risk of resistance. [29]
Other topical agents
Other topical agents include salicylic
acid and azelaic acid, which have
antibacterial, comedolytic, and antiinflammatory
properties.
They
are
considered
as
potential
first-line
monotherapy for female adult patients and a
good choice for maintenance therapy. [30] A
potential adverse effect of azelaic acid is
hypopigmentation, which might be helpful
in
treating
post-inflammatory
hyperpigmentation. Azelaic acid with 15%
gel formulation was found to be as effective
as topical benzoyl peroxide and clindamycin
for patients with mild to moderate acne. [31]
Systemic Agents
Isotretinoin
Oral isotretinoin works by affecting
the four pathophysiological pathways of AV
and reported to have a permanent remission
result on the disease course. It shows a 90%
reduction in sebum secretion and an almost
85% cure rate without relapse. [32] Its
mechanism of action is done by influencing
the G1-S phase of the cell cycle by
decreasing DNA synthesis, increasing p21
(encoded CDKN1A) protein expression, and
decreasing cyclin D1 protein expression.
Oral isotretinoin causes numerous adverse
effects, but severe effects rarely occur.
Although uncommon, depression is among
one of the adverse effects; thus, the use of
this regiment should be monitored closely.
[33]
Spironolactone
Spironolactone (SP) is a potassiumsparing diuretic, and selective aldosterone
blocker used off-label in dermatology for
the treatment of acne. In 1960, it received
initial approval by the FDA. [34] The
mechanism of action of SP is still unclear,
but is expected to affect androgen receptors
in the sebaceous glands and reduce sebum
production, causing an improvement of AV
symptoms. It also reduces the conversion of
weaker androgens to more potent androgens
in the peripheral tissues. The dose
recommendation of SP for acne is 25-200
mg/day divided into one to two doses. The
use of 50 mg SP twice a day on days 5
through 21 of women’s menstrual cycle
showed favorable clinical results with a low
incidence of side effects. [35] Salama et al.
reported that SP has antiandrogen properties
with a promising result in the treatment of
acne, especially in female patients.
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Febyan et.al. Acne vulgaris in adults: a brief review on diagnosis and management
However, the use of this preparation must
be careful because the systemic side effects
are often more detrimental than its clinical
benefits. [36]
Oral Antibiotics
Systemic antibiotics that are
commonly used in AV against P.acne
include tetracycline, erythromycin 500 mg
twice daily, clindamycin and doxycycline
100 mg twice daily. Unfortunately, the
broad spectrum and long-term use of
antibiotics over the years have led to the
emergence of resistant bacteria. [37]
Resistance to tetracycline and crossresistance to doxycycline are also common
and associated with a mutation in the 16S
ribosomal riziform of the small ribosomal
subunit in the equivalent base of E. coli
1058 (G-C). Resistance of erythromycin is
associated with point mutations in the genes
encoding subunit 23S of the ribosomal
RNA. [38] Meanwhile, reports of resistance
to azithromycin have not yet been found. [37]
Azithromycin 500 mg twice weekly for 12
weeks is safe and effective treatment of AV.
It reveals more potent efficacy if combined
with oral desloratadine. [39,40] Akter reported
that
the
combination
regimen
of
azithromycin and daily topical benzoyl
peroxide (4%) is indeed more efficient and
safe in the management of AV after 12
weeks of treatment. [41]
Oral Contraceptives
The FDA has approved the treatment
of AV related to hormonal pathology since
the 1990s. These regiments include the
combination of ethinyl estradiol and
norgestimate or the combination of
norethindrone acetate and ethinyl estradiol.
Oral
contraceptives
manipulate
the
androgen activity and have the same
properties as 25 mg of SP. Although the use
of hormonal modification may be helpful
for AV, dermatologists need to look for
endocrinopathies such as polycystic ovarian
syndrome (PCOS) that manifested as having
irregular menses, acne, infertility, and
obesity. It is recommended that these
hormonal therapies may only be considered
when first-line therapy failed. [42]
Future Development of Acne Treatment
One of the interesting findings about
the future management of AV is the
potential use of acne vaccines. As
mentioned above, AV is known to have a
multifactorial etiology. These vaccines are
supposed to induce the host immunity
against bacterial toxicity produced by
P.acne bacteria. An experimental study done
in animals showed a good outcome in
improving the immunity reaction in P. acneassociated inflammatory acnes. This vaccine
was also found to decrease the release of
cytokine production that is involved in acne
pathophysiology. [43]
CONCLUSION
This brief review highlights the
relevant clinical findings and pathology of
acne vulgaris as a chronic inflammatory
skin disease affecting the pilosebaceous
glands. It has multifactorial causes and
manifestations varying from the mild to
severe degree. Several highly effective
treatments of choice have been proposed as
a monotherapy or combination therapy to
reduce and prevent the occurrence of acne.
Appropriate clinical considerations are
needed for clinicians to ensure a
comprehensive approach in the management
of acne vulgaris.
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How to cite this article: Febyan, Wetarini K.
Acne vulgaris in adults: a brief review on
diagnosis and management. International
Journal of Research and Review. 2020; 7(5):
246-252.
******
International Journal of Research and Review (ijrrjournal.com)
Vol.7; Issue: 5; May 2020
252